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Weeds have a significant impact on vegetable production worldwide. These intensive cropping systems feature frequent tillage, fertilization and irrigation, providing ideal growing conditions for crops as well as certain weeds. Integrated weed management (IWM) can reduce reliance on herbicides by encouraging a systems approach to weed management. Using insights from global research and industry literature, we investigated the effectiveness of prevailing weed control methods, and evaluated emerging management practices and technologies for ongoing research and adoption. Weed control relies primarily on a relatively narrow range of herbicides as well as frequent tillage. Herbicides have negative impacts on soil, water and human health, while tillage impacts soil quality and function. Intensive cropping on smaller plots facilitates IWM, relying on multiple strategies including hand weeding, mulches, cover crops and cultural methods (e.g., crop rotations, timing). New herbicide options are suggested as an industry priority but are constrained by the lack of new chemistry and potential herbicide resistance. Refinement and adoption of non‐herbicide and emerging precision control methods into farm IWM in vegetables is more likely to be sustainable. This review is relevant to advanced vegetable production systems globally, but also to smallholder vegetable production in developing economies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same‐age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. DISCUSSION: Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI. [ABSTRACT FROM AUTHOR]

Background: Repetitive head impacts (RHI) from American football can lead to tau and non‐tau pathologies that might present as white matter hyperintensities (WMH) on FLAIR MRI. In 2022, we published a study in Alzheimer's & Dementia that examined WMH and their association with risk factors and clinical function in former elite football players. That study will be presented during this symposium along with new unpublished data that used imaging and fluid biomarkers to examine etiological correlates (tau, amyloid, neurodegeneration, axonal injury, neuroinflammation) of WMH in the same cohort. Methods: The multi‐site DIAGNOSE CTE Research Project recruited 180 football players and 60 asymptomatic males without RHI ("controls"), all 45‐74 years (Table 1). Participants completed MRI, lumbar puncture, and neuropsychological testing. Lesion Segmentation Toolbox estimated FLAIR WMH, FreeSurfer derived total cortical thickness, and a diffusion pipeline derived average global FA. CSF was analyzed for p‐tau181, Aβ1‐42, NfL, and sTREM2. Tobit regressions compared football players (n = 149) and controls (n = 53) on total and regional log‐WMH and estimated the effects of years of football and age of first exposure (AFE) to football on log‐WMH. Linear regressions evaluated log‐WMH and clinical associations in football players. Structural equation modeling (SEM) examined effects between log‐WMH and cortical thickness, FA, and the CSF biomarkers. Analyses accounted for age, race, revised Framingham Stroke Risk Profile (rFSRP), body mass index, APOE ε4, and evaluation site. Results: Alosco et al. (2022) found older (i.e., 60+) but not younger football players had greater total, frontal, temporal and parietal log‐WMH compared to controls (FDR‐adjusted p‐values<0.05; Table 2). Among older football players, younger AFE was associated with greater log‐WMH (beta = ‐0.13, 95% CI = ‐0.23,‐0.02). Greater log‐WMH corresponded to worse Trails A‐B (beta = ‐4.32, 95% CI = ‐8.59,‐0.05) and List Learning Long Delay scores (beta = ‐0.56, 95% CI = ‐0.93,‐0.19). Subsequent unpublished SEM analyses in football players (Figure 1) showed the following direct effects on log‐WMH: higher rFSRP, higher CSF p‐tau181, lower FA, and reduced cortical thickness. There were no indirect effects. Compared to controls, SEM associations were stronger in football players exception for cortical thickness. Conclusions: FLAIR WMH might have unique imaging characteristics, risk factors, and pathological underpinnings in people exposed to RHI. [ABSTRACT FROM AUTHOR]

Introduction: The presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players. Methods: A total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45–74 years) completed fluid‐attenuated inversion recovery magnetic resonance imaging, neuropsychological testing, and self‐report neuropsychiatric measures. Lesion Segmentation Toolbox estimated WMH. Analyses were performed in the total sample and stratified by age 60. Results: In older but not younger participants, former football players had greater total, frontal, temporal, and parietal log‐WMH compared to asymptomatic unexposed men. In older but not younger former football players, greater log‐WMH was associated with younger age of first exposure to football and worse executive function. Discussion: In older former football players, WMH may have unique presentations, risk factors, and etiologies. Highlights: Older but not younger former football players had greater total, frontal, temporal, and parietal lobe white matter hyperintensities (WMH) compared to same‐age asymptomatic unexposed men.Younger age of first exposure to football was associated with greater WMH in older but not younger former American football players.In former football players, greater WMH was associated with worse executive function and verbal memory. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease thought to be caused, in part, by repetitive head impact (RHI) exposure and characterized by phosphorylated tau deposition with varying patterns in the cerebral cortex. Flortaucipir tau PET data from the DIAGNOSE CTE Research Project was examined to investigate tau PET patterns and its relation to RHI exposure in former professional and college American football players. Method: In this study, 218 DIAGNOSE CTE participants, ages 45‐74, with flortaucipir PET were included; 104 were former National Football League players (PRO), 58 were former college football players (COL), and 56 had no history of contact sports, other exposure to RHI, or traumatic brain injury (UE). Regional flortaucipir uptake was quantified using established procedures for three previously defined statistical regions (superior frontal, left parietal, and medial temporal) and compared across the three groups. Association analyses were also performed to examine the relationship between flortaucipir uptake and exposure to RHI using the cumulative head impact index for linear acceleration g‐force (CHII‐G). The potential clinical utility of flortaucipir PET for CTE was also investigated by examining its ability to differentiate participants meeting criteria for traumatic encephalopathy syndrome (TES) and probable or possible level of certainty for CTE pathology from those who do not meet those criteria. Result: Significantly higher flortaucipir uptake was observed in former football players than in participants without RHI exposure, controlling for age and race for the superior frontal region (Fig. 1A), left parietal, and medial temporal regions. Association between regional flortaucipir uptake and CHII‐G was only observed in the superior frontal region in former players (PRO+COL) 60 years and older (Fig. 1B) and no association was observed in the full PRO+COL group. Flortaucipir PET was not able to differentiate TES groups in former football players (Fig. 1C). Conclusion: Elevated flortaucipir uptake was observed in former American football players to a group of unexposed men. The association between flortaucipir uptake and exposure to RHI may require a long latent period to manifest. Further investigation of more sensitive tau PET tracers and quantification techniques is warranted to better characterize CTE related tau pathology. [ABSTRACT FROM AUTHOR]

Neurological disorders are prevalent in horses, but their study is challenging due to anatomic constraints and the large body size; very few host‐specific in vitro models have been established to study these types of diseases, particularly from adult donor tissue. Here we report the generation of primary neuronal dorsal root ganglia (DRG) cultures from adult horses: the mixed, dissociated cultures, containing neurons and glial cells, remained viable for at least 90 days. Similar to DRG neurons in vivo, cultured neurons varied in size, and they developed long neurites. The mitochondrial movement was detected in cultured cells and was significantly slower in glial cells compared to DRG‐derived neurons. In addition, mitochondria were more elongated in glial cells than those in neurons. Our culture model will be a useful tool to study the contribution of axonal transport defects to specific neurodegenerative diseases in horses as well as comparative studies aimed at evaluating species‐specific differences in axonal transport and survival. [ABSTRACT FROM AUTHOR]

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age‐related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non‐negative matrix factorization (NMF) is a data‐driven approach that detects covarying patterns (components) within high‐dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self‐reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta‐Analysis) Military Brain Injury working group. Regressions were used to examine TBI‐ and mTBI‐related associations in NMF‐derived components while adjusting for age, sex, post‐traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age‐dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age‐dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans. [ABSTRACT FROM AUTHOR]

Background: Exposure to repetitive head impacts (RHI) is associated with an increased risk of later‐life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. Purpose: To investigate whether RHI exposure is associated with later‐life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. Study Type: Retrospective cohort study. Population: Seventy‐five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. Field Strength/Sequence: Diffusion‐weighted echo‐planar MRI at 3 T. Assessment: Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self‐report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free‐water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1‐7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT‐A) and Part B (TMT‐B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF‐A). Statistical Tests: Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. Results: RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT‐A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT‐B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT‐A (FA, r = 0.36; AD, r = 0.28), TMT‐B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29). Data Conclusion: These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players. Level of Evidence: 3 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

The US Naval Research Laboratory (NRL) has developed clock ensembles for a number of vital GNSS projects and services throughout the US and international community. Some efforts include algorithms for local realization of Coordinated Universal Time; participation in the upgrade of the Global Positioning System (GPS) system time; the initial implementation of a coherent geophysical reference time known as IGS Time (IGST); and development of various Department of Defense (DoD) capabilities for the dissemination and transfer of precise time. This paper will cover the major algorithm components that compute and maintain a robust and stable time reference for the most stringent applications mentioned here. These components include automated alert and response to clock anomalies and reduction of measurement weight in response to large clock measurement residuals. Both real and simulated data have been used to validate the ensemble algorithm and its products for reliable and robust usage in these environments. [ABSTRACT FROM AUTHOR]

Background: The teratogenic effects of prenatal alcohol exposure (PAE) have been extensively documented over the course of 45 years of research and psychiatric problems are pervasive in this population. In adults with PAE, suicidal risk is high but less is known about the suicidal risk in adolescents with fetal alcohol spectrum disorders (FASD). This study describes the prevalence of suicidal ideation and serious suicide attempts in a sample of 54 adolescents between the ages of 13 and 18 years with FASD. Methods: Adolescents were diagnosed with FASD using the Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. The Children's Interview for Psychiatric Syndromes was used to identify those adolescents who experienced suicidal ideation and/or who had made a serious suicide attempt in the last 12 months. Results: The prevalence of suicidal behaviors in this sample was high with 35.2% of teens reporting incidences of suicidal ideation and 13.0% reporting at least one serious suicide attempt in the past year. This finding is in contrast to the 17.2% and 2.4% for ideation and serious attempts, respectively, reported in the general U.S. adolescent population. Alarmingly, 29.2% of males with FASD reported a serious suicide attempt which was 19½ times higher than national norms for males. No females reported attempts. Number of home placements and the presence of a depressive disorder contributed to study outcomes. Conclusions: Findings demonstrate the significant risk for suicidality in this population, particularly adolescent males, and the need to assess and treat this life threatening behavior. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is characterized by perivascular foci of phosphorylated tau (p‐tau) notably in the depths of sulci, with varying patterns in the cerebral cortex. Prior studies show elevated flortaucipir (FTP) PET binding in former American professional football players(PRO). However, the association of p‐tau with clinical measures remains unclear using regional FTP SUVR as early signs of CTE related tau pathology. Graph theory (GT) takes advantages of the spatial variability in p‐tau load and allows the integration of regional measures to define GT based measures. Here we examine the GT based measures in two CTE cohorts to evaluate their utility in assessing p‐tau related pathology in CTE. Method: The graph procedure was optimized in FTP PET images in a group of 26 PRO with reported cognitive and/or behavorial symptoms and 30 asymptomatic controls without a history of traumatic brain injury (the DETECT Study) and identified the GT measure, entorhinal tau strength, as the target metric with the best group separation between PRO and controls. The optimized graph procedures were then applied to the DIAGNOSE CTE Research Project dataset (99 former PRO, 51 former college football players [COL], and 52 controls without exposure to repetitive head impacts [CTL]) and we examined entorhinal tau strength's ability to differentiate the exposure groups and relationship to consensus based diagnoses of Traumatic Encephalopathy Syndrome (TES), the clinical syndrome associated with CTE. Result: Entorhinal tau strength was significantly different among the three exposure groups (p=0.0001) similar to regional SUVR measures (Figure 1). Regional SUVR did not differentiate players (PRO+COL) with and without TES, while entorhinal tau strength approached although did not reach significance (Figure 2). Entorhinal tau strength is the only FTP measure that showed significant differences (p=0.006) between those players with cognitive impairment and players without (Figure 3). Conclusion: While there is still considerable overlap in between‐group measurements, GT based entorhinal tau strength, is potentially more sensitive in detecting tau changes in players with and without TES. Additional studies are necessary to clarify the value of this new measure in detecting underlying CTE pathology. [ABSTRACT FROM AUTHOR]

The next generation Global Positioning System (GPS) ground control segment will entail a number of GPS ground system upgrades from the existing ground control segment. One of these upgrades is the inclusion of a new modernized timescale algorithm used to generate GPS Time. The timescale is currently being designed as a separate modular unit (given the acronym ETF, or Ensemble Timescale Filter) within the ground system navigation package and is based upon a U-D Kalman Filter implementation that utilizes measurements of all clocks in the ground network and satellite constellation. The new ETF module will include a number of features that improve the stability of the GPS Time timescale and provide more user/operator autonomy to include: multi-weight clock weighting for better handling of mixed clock types in the same filter; automated clock break detection and handling; robust outlier and anomalous clock behavior mitigation; admission of multiple external timescale solutions, including alternate ETF realizations; and adaptive clock parameter estimation. The preliminary results presented in this paper demonstrate some of the performance capabilities and robustness characteristics of the ETF. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Antimalarial therapy during pregnancy poses important safety concerns due to potential teratogenicity and maternal physiological and biochemical changes during gestation. Piperaquine (PQ) has gained interest for use in pregnancy in response to increasing resistance towards sulfadoxine-pyrimethamine in sub-Saharan Africa. Coinfection with HIV is common in many developing countries, however, little is known about the impact of antiretroviral (ARV) mediated drug-drug interaction (DDI) on piperaquine pharmacokinetics during pregnancy. This study applied mechanistic pharmacokinetic modelling to predict pharmacokinetics in non-pregnant and pregnant patients, which was validated in distinct customised population groups from Thailand, Sudan and Papua New Guinea. In each population group, no significant differences in day 7 concentrations were observed during different gestational weeks (GW) (weeks 10-40), supporting the notion that piperaquine is safe throughout pregnancy with consistent pharmacokinetics, although possible teratogenicity may limit this. Antiretroviral-mediated DDIs (efavirenz and ritonavir) had moderate effects on piperaquine during different gestational weeks with a predicted AUCratio in the range 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir, respectively, over GW 10-40, with a reduction in circulating human serum albumin significantly reducing the number of subjects attaining the day 7 (post-dose) therapeutic efficacy concentrations under both efavirenz and ritonavir DDIs. This present model successfully mechanistically predicted the pharmacokinetics of piperaquine in pregnancy to be unchanged with respect to non-pregnant women, in the light of factors such as malaria/HIV co-infection. However, antiretroviral-mediated DDIs could significantly alter piperaquine pharmacokinetics. Further model refinement will include collation of relevant physiological and biochemical alterations common to HIV/malaria patients. [ABSTRACT FROM AUTHOR]

Astrocytes are now increasingly acknowledged as having fundamental and sophisticated roles in brain function and dysfunction. Unravelling the complex mechanisms that underlie human brain astrocyte-neuron interactions is therefore an essential step on the way to understanding how the brain operates. Insights into astrocyte function to date have almost exclusively been derived from studies conducted using murine or rodent models. Whilst these have led to significant discoveries, preliminary work with human astrocytes has revealed a hitherto unknown range of astrocyte types with potentially greater functional complexity and increased neuronal interaction with respect to animal astrocytes. It is becoming apparent, therefore, that many important functions of astrocytes will only be discovered by direct physiological interrogation of human astrocytes. Recent advancements in the field of stem cell biology have provided a source of human-based models. These will provide a platform to facilitate our understanding of normal astrocyte functions as well as their role in CNS pathology. A number of recent studies have demonstrated that stem cell-derived astrocytes exhibit a range of properties, suggesting that they may be functionally equivalent to their in vivo counterparts. Further validation against in vivo models will ultimately confirm the future utility of these stem cell-based approaches in fulfilling the need for human-based cellular models for basic and clinical research. In this review we discuss the roles of astrocytes in the brain and highlight the extent to which human stem cell-derived astrocytes have demonstrated functional activities that are equivalent to those observed in vivo. [ABSTRACT FROM AUTHOR]

Neurons rely heavily on axonal transport to deliver materials from the sites of synthesis to the axon terminals over distances that can be many centimetres long. KIF1A is the neuron-specific kinesin with the fastest reported anterograde motor activity. Previous studies have shown that KIF1A transports a subset of synaptic proteins, neurofilaments and dense-core vesicles. Using two-colour live imaging, we showed that beta-secretase 1 ( BACE1)- mCherry moves together with KIF1A-GFP in both the anterograde and retrograde directions in superior cervical ganglions ( SCG) neurons. We confirmed that KIF1A is functionally required for BACE1 transport by using KIF1A siRNA and a KIF1A mutant construct ( KIF1A-T312M) to impair its motor activity. We further identified several cargoes that have little or no co-migration with KIF1A-GFP and also move independently from BACE1-mCherry. Together, these findings support a primary role for KIF1A in the anterograde transport of BACE1 and suggest that axonally transported cargoes are sorted into different classes of carrier vesicles in the cell body and are transported by cargo-specific motor proteins through the axon. [ABSTRACT FROM AUTHOR]

Aim A causative relationship between acute coronary syndrome ( ACS) and periodontitis has yet to be defined. The aim of this study was to assess differences in levels of serum cytokines between individuals with or without ACS or periodontal comorbidity. Material and Methods In a case-control study, individuals with ACS (78 individuals, 10.3% females) and matching healthy controls (78 individuals, 28.2% females) were included. Medical and dental examinations were performed to diagnose ACS and periodontitis. Serum levels of cytokines were assessed, using Luminex technology. Results A diagnosis of periodontitis in the ACS and control group was diagnosed in 52.6% and 12.8% of the individuals, respectively. The unadjusted odds-ratio that individuals with ACS also had periodontitis was 7.5 (95% CI: 3.4, 16.8, p < 0.001). Independent of periodontal conditions, individuals with ACS had significantly higher serum levels of IL8 (mean: 44.3 and 40.0 pg/ml) and vascular endothelial growth factor ( VEGF) (mean: 82.3 and 55.3 pg/ml) than control individuals. A diagnosis of periodontitis made no difference in serum cytokine expressions. Conclusion Elevated serum levels of VEGF were associated with ACS. Serum cytokine expression in individuals with ACS is unrelated to periodontal conditions. [ABSTRACT FROM AUTHOR]

The diastereoselective cyclopropanation of various alkenes with diazoacetate derivatives can be achieved under mechanochemical conditions using metallic silver foil and a stainless-steel vial and ball system. This solvent-free method displays analogous reactivity and selectivity to solution-phase reactions without the need for slow diazoacetate addition or an inert atmosphere. The heterogeneous silver-foil catalyst system is easily recyclable without any appreciable loss of activity or selectivity being observed. The cyclopropanation products were obtained with excellent diastereoselectivities (up to 98:2 d.r.) and in high yields (up to 96 %). [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy ( CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE. [ABSTRACT FROM AUTHOR]

Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord blood, and other origins have recently received much attention as potential therapeutic agents with beneficial immunomodulatory and regenerative properties. In their native tissue environment, however, such cells also appear to have essential functions in building and supporting tumor microenvironments, providing metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied roles of these tissue-resident stroma-associated cells, synthesize recent and emerging discoveries, and discuss the role, potential, and clinical applications of MSCs in cancer and regenerative medicine. [ABSTRACT FROM AUTHOR]

At the catchment scale, soil moisture patterns have been observed to exhibit different types of dependence on topography. Some catchments have their wettest locations in the valley bottoms, while others have their wettest locations on hillslopes that are oriented away from the sun. Additionally, some catchments have soil moisture patterns that maintain a similar organization at all times (temporal stability), while other catchments have soil moisture patterns that change through time (temporal instability). Although these tendencies are well known, the reasons for their occurrence at a particular catchment are not well understood. In this paper, we investigate conditions under which different types of topographic dependence and different degrees of temporal instability can occur through the use of a new conceptual model. The type of topographic dependence and the degree of instability are quantified by two metrics that are also introduced in the paper, and the effects of soil, vegetation, and climatic parameters on these metrics are then evaluated. The evaluations indicate that saturated horizontal hydraulic conductivity, pore disconnectedness, and a vegetation evapotranspiration efficiency parameter have strong effects on the organization and instability of the soil moisture patterns. In contrast, annual potential evapotranspiration alone has less impact on the organization or its stability. [ABSTRACT FROM AUTHOR]

Soil moisture influences many hydrologic applications including agriculture, land management and flood prediction. Most remote-sensing methods that estimate soil moisture produce coarse resolution patterns, so methods are required to downscale such patterns to the resolutions required by these applications (e.g. 10- to 30-m grid cells). At such resolutions, topography is known to affect soil moisture patterns. Although methods have been proposed to downscale soil moisture based on topography, they usually require the availability of past high-resolution soil moisture patterns from the application region. The objective of this article is to determine whether a single topographic-based downscaling method can be used at multiple locations without relying on detailed local observations. The evaluated downscaling method is developed on the basis of empirical orthogonal function (EOF) analysis of space-time soil moisture data at a reference catchment. The most important EOFs are then estimated from topographic attributes, and the associated expansion coefficients are estimated on the basis of the spatial-average soil moisture. To test the portability of this EOF-based method, it is developed separately using four data sets (Tarrawarra, Tarrawarra 2, Cache la Poudre and Satellite Station), and the relationships that are derived from these data sets to estimate the EOFs and expansion coefficients are compared. In addition, each of these downscaling methods is applied not only for the catchment where it was developed but also to the other three catchments. The results suggest that the EOF downscaling method performs well for the location where it is developed, but its performance degrades when applied to other catchments. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Various types of stem cells have been shown to have beneficial effects on cardiac function. It is still debated whether fusion of injected stem cells with local resident cardiomyocytes is one of the mechanisms. To better understand the role of fusion in stem cell-based myocardial regeneration, the present study was designed to investigate the fate of human adipose tissue-derived stem cells (hASCs) fused with neonatal rat cardiomyocytes in vitro. hASCs labeled with the green fluorescent probe Vybrant DiO were cocultured with neonatal rat cardiomyocytes labeled with the red fluorescent probe Vybrant DiI and then treated with fusion-inducing hemagglutinating virus of Japan (HVJ). Cells that incorporated both red and green fluorescent signals were considered to be hASCs that had fused with rat cardiomyocytes. Fusion efficiency was 19.86 ± 4.84% at 5 d after treatment with HVJ. Most fused cells displayed cardiomyocyte-like morphology and exhibited spontaneous rhythmic contraction. Both immuno-fluorescence staining and lentiviral vector labeling showed that fused cells contained separate rat cardiomyocyte and hASC nuclei. Immunofluorescence staining assays demonstrated that human nuclei in fused cells still expressed the proliferation marker Ki67. In addition, hASCs fused with rat cardiomyocytes were positive for troponin I. Whole-cell voltage-clamp analysis demonstrated action potentials in beating fused cells. RT-PCR analysis using rat- or human-specific myosin heavy chain primers revealed that the myosin heavy-chain expression in fused cells was derived from rat cardiomyocytes. Real-time PCR identified expression of human troponin T in fused cells and the presence of rat cardiomyocytes induced a cardiomyogenic protein expression of troponin T in human ASCs. This study illustrates that hASCs exhibit both stem cell (proliferation) and cardiomyocyte properties (action potential and spontaneous rhythmic beating) after fusion with rat cardiomyocytes, supporting the theory that fusion, even if artificially induced in our study, could indeed be a mechanism for cardiomyocyte renewal in the heart. [ABSTRACT FROM AUTHOR]

Background and Purpose: N-hydroxylation of dapsone leads to the formation of the toxic hydroxylamines responsible for the clinical methaemoglobinaemia associated with dapsone therapy. Dapsone has been associated with decreased lifespan of erythrocytes, with consequences such as anaemia and morbidity in patients treated with dapsone for malaria. Here, we investigated how dapsone and/or its hydroxylamine derivative (DDS-NHOH) induced erythrocyte membrane alterations that could lead to premature cell removal.Experimental Approach: Erythrocytes from healthy donors were subjected to incubation with dapsone and DDS-NHOH for varying times and the band 3 protein tyrosine-phosphorylation process, band 3 aggregation, membrane alteration and IgG binding were all examined and compared with erythrocytes from two patients receiving dapsone therapy.Key Results: The hydroxylamine derivative, but not dapsone (the parent sulphone) altered membrane protein interactions, leading both to aggregation of band 3 protein and to circulating autologous antibody binding, shown in erythrocytes from patients receiving dapsone therapy. The band 3 tyrosine-phosphorylation process can be used as a diagnostic system to monitor membrane alterations both in vitro, assessing concentration and time-dependent effects of DDS-NHOH treatment, and in vivo, evaluating erythrocytes from dapsone-treated patients, in resting or oxidatively stimulated conditions.Conclusions and Implications: DDS-NHOH-induced alterations of human erythrocytes can be directly monitored in vitro by tyrosine-phosphorylation level and formation of band 3 protein aggregates. The latter, together with antibody-mediated labelling of erythrocytes, also observed after clinical use of dapsone, may lead to shortening of erythrocyte lifespan. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a cell-autonomous process that eliminates large quantities of misfolded, newly synthesized protein, and is thus essential for the survival of any basic eukaryotic cell. Accordingly, the proteins involved and their interaction partners are well conserved from yeast to mammals, and Saccharomyces cerevisiae is widely used as a model system with which to investigate this fundamental cellular process. For example, valosin-containing protein (VCP) and its yeast homologue cell division cycle protein 48 (Cdc48p), which help to direct polyubiquitinated proteins for proteasome-mediated degradation, interact with an equivalent group of ubiquitin ligases in mouse and in S. cerevisiae. A conserved structural motif for cofactor binding would therefore be expected. We report a VCP-binding motif (VBM) shared by mammalian ubiquitin ligase E4b (Ube4b)–ubiquitin fusion degradation protein 2a (Ufd2a), hydroxymethylglutaryl reductase degradation protein 1 (Hrd1)–synoviolin and ataxin 3, and a related sequence in Mr 78 000 glycoprotein–Amfr with slightly different binding properties, and show that Ube4b and Hrd1 compete for binding to the N-terminal domain of VCP. Each of these proteins is involved in ERAD, but none has an S. cerevisiae homologue containing the VBM. Some other invertebrate model organisms also lack the VBM in one or more of these proteins, in contrast to vertebrates, where the VBM is widely conserved. Thus, consistent with their importance in ERAD, evolution has developed at least two ways to bring these proteins together with VCP–Cdc48p. However, the differing molecular architecture of VCP–Cdc48p complexes indicates a key point of divergence in the molecular details of ERAD mechanisms. [ABSTRACT FROM AUTHOR]